In a recent article (Latman, N. S. 1983, Amer. J. Med. 74: 957-960), one of the co-inventors of the present application, provides a review of the evidence which suggests possible anti-inflammatory activity of some of the sex steroid hormones, progesterone and some of the estrogens. Specifically the observations included the fact that the symptoms of rheumatoid arthritis are significantly reduced during the post-ovulatory phase of the menstrual cycle; that pregnancy usually results in symptomatic relief of rheumatoid arthritis; that there is a reduction in the incidence of rheumatoid arthritis by approximately 50% in women taking an oral contraceptive; and that progesterone and some of the estrogen treatments reduce symptoms of inflammation and arthritis in several animal models. It was thus suggested that progesterone and at least some of the estrogens may exhibit anti-inflammatory activity. This activity is believed to be associated with molecular structural characteristics, but the problem remains to identify the structural characteristics which are effective within certain steroidal hormones and their metabolites and derivatives which may exhibit a high degree of anti-inflammatory activity with a minimum of estrogenic and/or mineralocorticoid activity.
A number of steroids have been tested over the years as possibly having some anti-inflammatory effects, with many being ultimately found to have little or no anti-inflammatory effect. In short, it has been long recognized that the fact that a chemical may be a steroid is not necessarily an indication that it may have any anti-inflammatory effect. Example of steroids which appear to exhibit no anti-inflammatory activity or may exhibit pro-inflammatory activity include aldosterone, 11-deoxycorticosterone (Bentley, P. J. "Endocrine Pharmacology" 1980. Cambridge University Press, Cambridge), 11-desoxycortisol, and tetrahydrocortisol (Haynes, R. C. and F. Murad. "Adrenocorticotropic Hormone: Adrenocortical Steroids and Their Synthetic Analogs: Inhibitors of Adrenocortical steroid biosynthesis." in Gilman, A. G. et al (Editors). "The Pharmacological Basis of Therapeutics." 7th edition, 1985. MacMillan Publishing Co., New York.)